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Intrauterine fetal transfusion of red blood cells

INTRODUCTION

The infusion of red blood cells (RBCs) into the fetus is one of the most successful means of in utero therapy. Although never studied in randomized trials, there is no doubt that this technique has contributed to survival of the severely anemic fetus. Universal use of Rh(D) immune globulin has dramatically reduced the need for intrauterine transfusion; however, the procedure continues to be an essential modality for treatment of severe fetal anemia from a variety of causes.

HISTORY

Sir William Liley first introduced the concept of intrauterine transfusion (IUT). While working in New Zealand, he learned from a visiting fellow that RBCs infused into the peritoneal cavity of African children with sickle cell disease appeared to migrate into the intravascular space and correct their anemia [1]. Liley postulated that peritoneal infusion (IPT) of RBCs could also be used to transfuse the severely anemic fetus. Since ultrasonography was not yet available, these early procedures were 'guided' by radiographs or fluoroscopy. Fetal position was determined by a variety of techniques, such as using radiopaque dyes to delineate fetal bowel, placing metal markers on the maternal abdomen to indicate fetal position, and inserting needles to immobilize the fetus.

Static gray scale ultrasonography was first used in conjunction with IUT in 1975, and replaced by real-time ultrasonography in 1977. The next major advance was in 1981 when an intravascular transfusion (IVT) was performed by inserting the transfusion needle directly into a fetal vessel on the placental plate [2]. Currently, the standard method of fetal transfusion uses an umbilical vessel or the intrahepatic portion of the umbilical vein for direct access to the fetal vasculature.

PATIENT SELECTION

General approach — Intrauterine transfusion of RBCs is indicated to prevent fetal death from severe anemia. The procedure is generally limited to fetuses between 18 and 35 weeks of gestation because of technical limitations before 18 weeks and excessive fetal risk compared with delivery and postnatal transfusion after 35 weeks (see 'Gestational age at first transfusion' below).

Normal fetal hemoglobin concentration increases linearly during pregnancy, from about 10 to 11 g/dL at 17 weeks to about 14 to 15 g/dL at term, one standard deviation is approximately 1 g/dL (table 1) [3-5]. Severe fetal anemia has been defined in a variety of ways:

                                         

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Literature review current through: Aug 2014. | This topic last updated: Sep 30, 2013.
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References
Top
  1. LILEY AW. INTRAUTERINE TRANSFUSION OF FOETUS IN HAEMOLYTIC DISEASE. Br Med J 1963; 2:1107.
  2. Rodeck CH, Kemp JR, Holman CA, et al. Direct intravascular fetal blood transfusion by fetoscopy in severe Rhesus isoimmunisation. Lancet 1981; 1:625.
  3. Nicolaides KH, Soothill PW, Clewell WH, et al. Fetal haemoglobin measurement in the assessment of red cell isoimmunisation. Lancet 1988; 1:1073.
  4. Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000; 342:9.
  5. Forestier F, Daffos F, Catherine N, et al. Developmental hematopoiesis in normal human fetal blood. Blood 1991; 77:2360.
  6. von Kaisenberg CS, Jonat W. Fetal parvovirus B19 infection. Ultrasound Obstet Gynecol 2001; 18:280.
  7. Carr S, Rubin L, Dixon D, et al. Intrauterine therapy for homozygous alpha-thalassemia. Obstet Gynecol 1995; 85:876.
  8. Ng PC, Fok TF, Lee CH, et al. Is homozygous alpha-thalassaemia a lethal condition in the 1990s? Acta Paediatr 1998; 87:1197.
  9. Hayward A, Ambruso D, Battaglia F, et al. Microchimerism and tolerance following intrauterine transplantation and transfusion for alpha-thalassemia-1. Fetal Diagn Ther 1998; 13:8.
  10. Wang C, Ryan G. Transfusion medicine illustrated: Intrauterine transfusion for homozygous alpha(0) thalassemia reverses hydrops fetalis. Transfusion 2009; 49:1043.
  11. Remacha AF, Badell I, Pujol-Moix N, et al. Hydrops fetalis-associated congenital dyserythropoietic anemia treated with intrauterine transfusions and bone marrow transplantation. Blood 2002; 100:356.
  12. Ogburn PL Jr, Ramin KD, Danilenko-Dixon D, et al. In utero erythrocyte transfusion for fetal xerocytosis associated with severe anemia and non-immune hydrops fetalis. Am J Obstet Gynecol 2001; 185:238.
  13. Quarello E, Stirnemann J, Nassar M, et al. Outcome of anaemic monochorionic single survivors following early intrauterine rescue transfusion in cases of feto-fetal transfusion syndrome. BJOG 2008; 115:595.
  14. Herway C, Johnson A, Moise K, Moise KJ Jr. Fetal intraperitoneal transfusion for iatrogenic twin anemia-polycythemia sequence after laser therapy. Ultrasound Obstet Gynecol 2009; 33:592.
  15. Guidelines on gamma irradiation of blood components for the prevention of transfusion-associated graft-versus-host disease. BCSH Blood Transfusion Task Force. Transfus Med 1996; 6:261.
  16. Vengelen-Tyler, V. Technical Manual of the American Association of Blood Banks. Bethesda, Maryland: American Association of Blood Banks, 1999.
  17. Viëtor HE, Kanhai HH, Brand A. Induction of additional red cell alloantibodies after intrauterine transfusions. Transfusion 1994; 34:970.
  18. Schonewille H, Klumper FJ, van de Watering LM, et al. High additional maternal red cell alloimmunization after Rhesus- and K-matched intrauterine intravascular transfusions for hemolytic disease of the fetus. Am J Obstet Gynecol 2007; 196:143.e1.
  19. Watson WJ, Wax JR, Miller RC, Brost BC. Prevalence of new maternal alloantibodies after intrauterine transfusion for severe Rhesus disease. Am J Perinatol 2006; 23:189.
  20. el-Azeem SA, Samuels P, Rose RL, et al. The effect of the source of transfused blood on the rate of consumption of transfused red blood cells in pregnancies affected by red blood cell alloimmunization. Am J Obstet Gynecol 1997; 177:753.
  21. Dodd JM, Windrim RC, van Kamp IL. Techniques of intrauterine fetal transfusion for women with red-cell isoimmunisation for improving health outcomes. Cochrane Database Syst Rev 2012; 9:CD007096.
  22. Harman CR, Bowman JM, Manning FA, Menticoglou SM. Intrauterine transfusion--intraperitoneal versus intravascular approach: a case-control comparison. Am J Obstet Gynecol 1990; 162:1053.
  23. Fox C, Martin W, Somerset DA, et al. Early intraperitoneal transfusion and adjuvant maternal immunoglobulin therapy in the treatment of severe red cell alloimmunization prior to fetal intravascular transfusion. Fetal Diagn Ther 2008; 23:159.
  24. Lewis M, Bowman JM, Pollock J, Lowen B. Absorption of red cells from the peritoneal cavity of an hydropic twin. Transfusion 1973; 13:37.
  25. Creasman WT, Duggan ER, Lund CJ. Absorption of transfused chromium-labeled erythrocytes from the fetal peritoneal cavity in hydrops fetalis. Am J Obstet Gynecol 1966; 94:586.
  26. Taylor WW, Scott DE, Pritchard JA. Fate of compatible adult erythrocytes in the fetal peritoneal cavity. Obstet Gynecol 1966; 28:175.
  27. Westgren M, Selbing A, Stangenberg M. Fetal intracardiac transfusions in patients with severe rhesus isoimmunisation. Br Med J (Clin Res Ed) 1988; 296:885.
  28. Weiner CP, Wenstrom KD, Sipes SL, Williamson RA. Risk factors for cordocentesis and fetal intravascular transfusion. Am J Obstet Gynecol 1991; 165:1020.
  29. Van Kamp IL, Klumper FJ, Oepkes D, et al. Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization. Am J Obstet Gynecol 2005; 192:171.
  30. Ellison JP. The nerves of the umbilical cord in man and the rat. Am J Anat 1971; 132:53.
  31. Nicolini U, Santolaya J, Ojo OE, et al. The fetal intrahepatic umbilical vein as an alternative to cord needling for prenatal diagnosis and therapy. Prenat Diagn 1988; 8:665.
  32. Giannakoulopoulos X, Sepulveda W, Kourtis P, et al. Fetal plasma cortisol and beta-endorphin response to intrauterine needling. Lancet 1994; 344:77.
  33. Nicolini U, Nicolaidis P, Fisk NM, et al. Fetal blood sampling from the intrahepatic vein: analysis of safety and clinical experience with 214 procedures. Obstet Gynecol 1990; 76:47.
  34. Moise KJ Jr, Carpenter RJ Jr, Kirshon B, et al. Comparison of four types of intrauterine transfusion: effect on fetal hematocrit. Fetal Ther 1989; 4:126.
  35. Nicolini U, Kochenour NK, Greco P, et al. When to perform the next intra-uterine transfusion in patients with Rh allo-immunization: combined intravascular and intraperitoneal transfusion allows longer intervals. Fetal Ther 1989; 4:14.
  36. Welch R, Rampling MW, Anwar A, et al. Changes in hemorheology with fetal intravascular transfusion. Am J Obstet Gynecol 1994; 170:726.
  37. Dildy GA 3rd, Smith LG Jr, Moise KJ Jr, et al. Porencephalic cyst: a complication of fetal intravascular transfusion. Am J Obstet Gynecol 1991; 165:76.
  38. Drew JH, Guaran RL, Cichello M, Hobbs JB. Neonatal whole blood hyperviscosity: the important factor influencing later neurologic function is the viscosity and not the polycythemia. Clin Hemorheol Microcirc 1997; 17:67.
  39. Giannina G, Moise KJ Jr, Dorman K. A simple method to estimate volume for fetal intravascular transfusions. Fetal Diagn Ther 1998; 13:94.
  40. Mandelbrot L, Daffos F, Forestier F, et al. Assessment of fetal blood volume for computer-assisted management of in utero transfusion. Fetal Ther 1988; 3:60.
  41. Moise KJ Jr, Mari G, Fisher DJ, et al. Acute fetal hemodynamic alterations after intrauterine transfusion for treatment of severe red blood cell alloimmunization. Am J Obstet Gynecol 1990; 163:776.
  42. Radunovic N, Lockwood CJ, Alvarez M, et al. The severely anemic and hydropic isoimmune fetus: changes in fetal hematocrit associated with intrauterine death. Obstet Gynecol 1992; 79:390.
  43. Bowman JM. The management of Rh-Isoimmunization. Obstet Gynecol 1978; 52:1.
  44. Canlorbe G, Macé G, Cortey A, et al. Management of very early fetal anemia resulting from red-cell alloimmunization before 20 weeks of gestation. Obstet Gynecol 2011; 118:1323.
  45. Klumper FJ, van Kamp IL, Vandenbussche FP, et al. Benefits and risks of fetal red-cell transfusion after 32 weeks gestation. Eur J Obstet Gynecol Reprod Biol 2000; 92:91.
  46. Ruma MS, Moise KJ Jr, Kim E, et al. Combined plasmapheresis and intravenous immune globulin for the treatment of severe maternal red cell alloimmunization. Am J Obstet Gynecol 2007; 196:138.e1.
  47. Howe DT, Michailidis GD. Intraperitoneal transfusion in severe, early-onset Rh isoimmunization. Obstet Gynecol 2007; 110:880.
  48. Daffos F, Forestier F, Mac Aleese J, et al. Fetal curarization for prenatal magnetic resonance imaging. Prenat Diagn 1988; 8:312.
  49. Bernstein HH, Chitkara U, Plosker H, et al. Use of atracurium besylate to arrest fetal activity during intrauterine intravascular transfusions. Obstet Gynecol 1988; 72:813.
  50. Mouw RJ, Klumper F, Hermans J, et al. Effect of atracurium or pancuronium on the anemic fetus during and directly after intravascular intrauterine transfusion. A double blind randomized study. Acta Obstet Gynecol Scand 1999; 78:763.
  51. Lobato G, Soncini CS. Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization. Fetal Diagn Ther 2008; 24:349.
  52. Egberts J, van Kamp IL, Kanhai HH, et al. The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal. Br J Obstet Gynaecol 1997; 104:818.
  53. Lobato G, Soncini CS. Fetal hematocrit decrease after repeated intravascular transfusions in alloimmunized pregnancies. Arch Gynecol Obstet 2007; 276:595.
  54. Egberts J, Hardeman MR, Luykx LM. Decreased deformability of donor red blood cells after intrauterine transfusion in the human fetus: possible reason for their reduced life span? Transfusion 2004; 44:1231.
  55. Mari G, Detti L, Oz U, et al. Accurate prediction of fetal hemoglobin by Doppler ultrasonography. Obstet Gynecol 2002; 99:589.
  56. Scheier M, Hernandez-Andrade E, Fonseca EB, Nicolaides KH. Prediction of severe fetal anemia in red blood cell alloimmunization after previous intrauterine transfusions. Am J Obstet Gynecol 2006; 195:1550.
  57. Detti L, Oz U, Guney I, et al. Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization. Am J Obstet Gynecol 2001; 185:1048.
  58. Moise KJ Jr. The usefulness of middle cerebral artery Doppler assessment in the treatment of the fetus at risk for anemia. Am J Obstet Gynecol 2008; 198:161.e1.
  59. Mari, G, Zimmerman, R, Segata, M. Am J Obstet Gynecol 2005; 191:S149.
  60. Stefos T, Cosmi E, Detti L, Mari G. Correction of fetal anemia on the middle cerebral artery peak systolic velocity. Obstet Gynecol 2002; 99:211.
  61. Trevett TN Jr, Dorman K, Lamvu G, Moise KJ Jr. Antenatal maternal administration of phenobarbital for the prevention of exchange transfusion in neonates with hemolytic disease of the fetus and newborn. Am J Obstet Gynecol 2005; 192:478.
  62. Lepercq J, Poissonnier MH, Coutanceau MJ, et al. Management and outcome of fetomaternal Rh alloimmunization in twin pregnancies. Fetal Diagn Ther 1999; 14:26.
  63. Cariappa R, Parvin CA, Gronowski AM. Bilirubin in amniotic fluid does not interfere with the Abbott TDx FLM II assay. Clin Chem 2003; 49:986.
  64. Watts DH, Luthy DA, Benedetti TJ, et al. Intraperitoneal fetal transfusion under direct ultrasound guidance. Obstet Gynecol 1988; 71:84.
  65. Queenan JT. Intrauterine transfusion. A cooperative study. Am J Obstet Gynecol 1969; 104:397.
  66. Friesen RF. Complications of intrauterine transfusion. Clin Obstet Gynecol 1971; 14:572.
  67. Keckstein G, Tschürtz S, Schneider V, et al. Umbilical cord haematoma as a complication of intrauterine intravascular blood transfusion. Prenat Diagn 1990; 10:59.
  68. Ghi T, Brondelli L, Simonazzi G, et al. Sonographic demonstration of brain injury in fetuses with severe red blood cell alloimmunization undergoing intrauterine transfusions. Ultrasound Obstet Gynecol 2004; 23:428.
  69. Nicolini U, Kochenour NK, Greco P, et al. Consequences of fetomaternal haemorrhage after intrauterine transfusion. BMJ 1988; 297:1379.
  70. Evans DG, Lyon AJ. Fatal congenital cytomegalovirus infection acquired by an intra-uterine transfusion. Eur J Pediatr 1991; 150:780.
  71. Schumacher B, Moise KJ Jr. Fetal transfusion for red blood cell alloimmunization in pregnancy. Obstet Gynecol 1996; 88:137.
  72. van Kamp IL, Klumper FJ, Meerman RH, et al. Treatment of fetal anemia due to red-cell alloimmunization with intrauterine transfusions in the Netherlands, 1988-1999. Acta Obstet Gynecol Scand 2004; 83:731.
  73. Poissonnier MH, Picone O, Brossard Y, Lepercq J. Intravenous fetal exchange transfusion before 22 weeks of gestation in early and severe red-cell fetomaternal alloimmunization. Fetal Diagn Ther 2003; 18:467.
  74. Yinon Y, Visser J, Kelly EN, et al. Early intrauterine transfusion in severe red blood cell alloimmunization. Ultrasound Obstet Gynecol 2010; 36:601.
  75. Saade GR, Moise KJ, Belfort MA, et al. Fetal and neonatal hematologic parameters in red cell alloimmunization: predicting the need for late neonatal transfusions. Fetal Diagn Ther 1993; 8:161.
  76. De Boer IP, Zeestraten EC, Lopriore E, et al. Pediatric outcome in Rhesus hemolytic disease treated with and without intrauterine transfusion. Am J Obstet Gynecol 2008; 198:54.e1.
  77. Janssens HM, de Haan MJ, van Kamp IL, et al. Outcome for children treated with fetal intravascular transfusions because of severe blood group antagonism. J Pediatr 1997; 131:373.
  78. Hudon L, Moise KJ Jr, Hegemier SE, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease. Am J Obstet Gynecol 1998; 179:858.
  79. Dembinski J, Haverkamp F, Maara H, et al. Neurodevelopmental outcome after intrauterine red cell transfusion for parvovirus B19-induced fetal hydrops. BJOG 2002; 109:1232.
  80. Moise, KJ, Whitecar PW. Antenatal therapy for haemolytic disease of the fetus and newborn. In: Alloimmune disorders in pregnancy. Anaemia, thrombocytopenia and neutropenia in the fetus and newborn, Hadley, A, Soothill, P (Eds), Cambridge University Press, Cambridge, UK 2002.
  81. Harper DC, Swingle HM, Weiner CP, et al. Long-term neurodevelopmental outcome and brain volume after treatment for hydrops fetalis by in utero intravascular transfusion. Am J Obstet Gynecol 2006; 195:192.
  82. Grab D, Paulus WE, Bommer A, et al. Treatment of fetal erythroblastosis by intravascular transfusions: outcome at 6 years. Obstet Gynecol 1999; 93:165.
  83. Lindenburg IT, Smits-Wintjens VE, van Klink JM, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study. Am J Obstet Gynecol 2012; 206:141.e1.